Nucleophilic Amination of Methoxy Arenes Promoted by a Sodium Hydride/Iodide Composite

Abstract

A method for the nucleophilic amination of methoxy arenes was established by using sodium hydride (NaH) in the presence of lithium iodide (LiI). This method offers an efficient route to benzannulated nitrogen heterocycles. Mechanistic studies showed that the reaction proceeds through an unusual concerted nucleophilic aromatic substitution.

Concerted Nucleophilic Aromatic Substitution Reactions

“…Ritter's studies [53][54][55][56] on the deoxyfluorination of phenols. [58] This methodology was compatible with electron-donating and electron-withdrawing substituents on the methoxyarene.…”

“…have recently reported remarkable reactions of a sodium hydride–lithium iodide composite. One of the reaction types reported by that team promoted the nucleophilic amination of methoxyarenes 117 , via intra‐ (Scheme ) and intermolecular (Scheme ) reactions . This methodology was compatible with electron‐donating and electron‐withdrawing substituents on the methoxyarene.…”

Konzertierte nukleophile aromatische Substitutionen

“…haben kürzlich über bemerkenswerte Reaktionen von Natriumhydrid/Lithiumiodid‐Gemische berichtet. Einer der beschriebenen Reaktionstypen beinhaltete die nukleophile Aminierung von Methoxyaromaten 117 in intra‐ (Schema ) und intermolekularen Prozessen (Schema ) . Dieses Protokoll war kompatibel mit elektronenschiebenden und elektronenziehenden Substituenten am Methoxyaromaten.…”

Recent Progress in Amination Enabled by Transition-Metal-Free C(sp2)–O/C(sp2)–S Bond Cleavage Strategy

“…18 In 2017, Takita, Chiba, and co-workers reported an unprecedented example of the intramolecular nucleophilic amination of methoxyarenes by a tethered amine moiety and intermolecular amination of methoxyarenes in the presence of a sodium hydride-iodide composite, formed from solvothermal treatment of sodium hydride with lithium iodide, at 90 °C (Scheme 4a). 19 The development of this approach enabled the facile production of benzannulated saturated nitrogen heterocycles, which are found in numerous natural alkaloids and potent pharmaceuticals. The substrate scope of this work was reasonably good, but the functional group compatibility was not satisfying, only inert ethers or tertiary amine were tolerated.…”